@article {1433723,
	title = {Lung CD8+ T cells in COPD have increased expression of bacterial TLRs},
	journal = {Respir Res},
	volume = {14},
	year = {2013},
	month = {2013 Feb 01},
	pages = {13},
	abstract = {BACKGROUND: Toll-like receptors (TLRs) on T cells can modulate their responses, however, the extent and significance of TLR expression by lung T cells, NK cells, or NKT cells in chronic obstructive pulmonary disease (COPD) is unknown.

METHODS: Lung tissue collected from clinically-indicated resections (n = 34) was used either: (a) to compare the expression of TLR1, TLR2, TLR2/1, TLR3, TLR4, TLR5, TLR6 and TLR9 on lung CD8+ T cells, CD4+ T cells, NK cells and NKT cells from smokers with or without COPD; or (b) to isolate CD8+ T cells for culture with anti-CD3ε without or with various TLR ligands. We measured protein expression of IFN-γ, TNF-α, IL-13, perforin, granzyme A, granzyme B, soluble FasL, CCL2, CCL3, CCL4, CCL5, CCL11, and CXCL9 in supernatants.

RESULTS: All the lung subsets analyzed demonstrated low levels of specific TLR expression, but the percentage of CD8+ T cells expressing TLR1, TLR2, TLR4, TLR6 and TLR2/1 was significantly increased in COPD subjects relative to those without COPD. In contrast, from the same subjects, only TLR2/1 and TLR2 on lung CD4+ T cells and CD8+ NKT cells, respectively, showed a significant increase in COPD and there was no difference in TLR expression on lung CD56+ NK cells. Production of the Tc1 cytokines IFN-γ and TNF-α by lung CD8+ T cells were significantly increased via co-stimulation by Pam3CSK4, a specific TLR2/1 ligand, but not by other agonists. Furthermore, this increase in cytokine production was specific to lung CD8+ T cells from patients with COPD as compared to lung CD8+ T cells from smokers without COPD.

CONCLUSIONS: These data suggest that as lung function worsens in COPD, the auto-aggressive behavior of lung CD8+ T cells could increase in response to microbial TLR ligands, specifically ligands against TLR2/1.},
	keywords = {Aged, CD8-Positive T-Lymphocytes, Cells, Cultured, Female, Gene Expression Regulation, Bacterial, Humans, Lung, Male, Middle Aged, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Toll-Like Receptors},
	issn = {1465-993X},
	doi = {10.1186/1465-9921-14-13},
	author = {Freeman, Christine M and Martinez, Fernando J and Han, MeiLan K and Washko, George R and McCubbrey, Alexandra L and Chensue, Stephen W and Arenberg, Douglas A and Meldrum, Catherine A and McCloskey, Lisa and Curtis, Jeffrey L}
}